Molecular Stem Cell Biology Laboratory

The laboratory has four main research branches: 

1. Lentiviral Gene therapy: we develop innovative lentiviral gene therapy strategies for metabolic disorders with a focus on lysosomal storage disorders. This consists of engineering ex vivo bone marrow stem cells with lentiviral vectors to reintroduce a therapeutic gene. We have modified this strategy to tackle difficult-to-reach tissues, such as the brain and muscles. This has resulted in successful pre-clinical developments for Pompe disease and Hunter disease, while new efforts are being made for CLN2 and CLN3. Importantly, we have establishedLentiCure, a non-profit company that aims at commercial development of gene therapies for reasonable and transparent pricing. 
2. Muscle-on-chip: Skeletal muscle is the largest organ and a crucial metabolic hub of the body. Traditional cell culture methods fail to reproduce the complex three-dimensional architecture of muscle and its function of enabling movement through contraction. Our lab developed a pipeline to generate human contractile 3D Tissue Engineered Skeletal Muscles (3D-TESMs) in vitro, using myogenic progenitor cells derived from hiPSCs. Using rapid prototyping, bio/micro-fabrication, and tissue-engineering we validated muscle-on-chip platforms to model skeletal muscle functionality and disease. The 3D-TESMs are currently used to study neuromuscular and metabolic diseases such as Pompe disease and as a platform to screen therapeutic strategies.
3. RNA therapeutics: Antisense oligonucleotides (ASOs) enable precise modulation of gene expression and RNA processing, offering therapeutic potential for genetic and metabolic diseases. We optimize ASO-based strategies targeting molecular defects in lysosomal and metabolic disorders. Advanced conjugation technologies and delivery enhancements such as the use of lipid nanoparticles are employed to improve potency, stability, and tissue penetration, particularly in challenging organs such as muscle tissue, which is our main focus. This approach has yielded promising preclinical results for Pompe disease, with ongoing efforts focused on expanding the pipeline, refining splicing modulation and upregulation strategies, and translating candidates toward clinical application.
4. Muscle stem cells and regeneration: Skeletal muscle is a highly regenerative tissue capable of repairing after damage. This potential is dependent on muscle stem cells, called satellite cells. Satellite cells are quiescent and become activated upon damage. Our lab has shown that the regenerative capacity of skeletal muscle is affected in Pompe disease, in line with observations in other neuromuscular disorders. Our goal is to understand why muscle regeneration becomes defective as disease progresses and to use this knowledge to develop clinical approaches that counteract this. These approaches include stimulating endogenous muscle repair and implementing stem cell replacement strategies.

Dr. W.W.M. Pim Pijnappel, Professor, Head Molecular Stem Cell Biology group
Dr. Gerben Schaaf, Assistant Professor
Dr. Atze Bergsma, Assistant Professor
Dr. Fabio Catalano, Post-doctoral researcher
Dr. Alessandro Iuliano, Post-doctoral researcher
Giacomo Zundo, MSc PhD student
Dejan Stevic, MSc, PhD student
Max Hennink, Msc, PhD student
Miro Weitzel, PhD student
Federico Silvestri, MSc, PhD student
Carlo Castiglione, MSc, PhD Student
Tess van der Loo, MSc, PhD student
Davey vander Horst, MSc PhD student (PI: Dr. George Ruijter, Clinical Genetics)
Tessa Huizer, BSc, technician
Anjali Bholasing, BSc, technician
WassimOuhammou, BSc, technician
Jiaxin Wu, MSc, technician